Cholescintigraphy in the detection of cholelithiasis: a review of 23 cases and a case report demonstrating the sequential evolution of the appearance of the gallbladder defect

Cholescintigraphy of cholelithiasis has been reported as a defect or photon deficient area in the gallbladder. We present the case of a patient with gallstones whose cholescintigraphic study showed a sequential evaluation of the scan appearance from a defect, to a septation, a hole, and finally a filled-in appearance. Cholescintigrams and histopathologic findings after cholecystectomy of another 22 patients with cholelithiasis were also retrospectively reviewed. The results of the study concluded that: cholelithiasis is rarely demonstrated by cholescintigraphy and nonvisualization of the gallbladder may be due to acute or chronic cholecystitis associated with cholelithiasis.     

Cholescintigraphy in the detection of cholelithiasis: A review of 23 cases and a case report demonstrating the sequential evolution of the appearance of the gallbladder defect

Cholescintigraphy of cholelithiasis has been reported as a defect or photon deficient area in the gallbladder. We present the case of a patient with gallstones whose cholescintigraphic study showed a sequential evaluation of the scan appearance from a defect, to a septation, a hole, and finally a filled-in appearance. Cholescintigrams and histopathologic findings after cholecystectomy of another 22 patients with cholelithiasis were also retrospectively reviewed. The results of the study concluded that: (1) cholelithiasis is rarely demonstrated by cholescintigraphy and (2) nonvisualization of the gallbladder may be due to acute or chronic cholecystitis associated with cholelithiasis.     

Prognostic value and pathophysiologic significance of the rim sign in cholescintigraphy

This study reviews 27 patients with nonvisualization of the gallbladder on cholescintigraphy. The preoperative diagnosis of acute cholecystitis was confirmed pathologically in 23. A rim of increased hepatic activity (RIHA) adjacent to the gallbladder fossa was seen throughout the study in 35% with acute cholecystitis and in no patients with chronic cholecystitis. Nine patients with "complicated" cholecystitis (defined pathologically as a late stage of the spectrum of acute cholecystitis) had a positive RIHA in contrast to no patients with "noncomplicated acute cholecystitis" (p less than 0.05). The sensitivity/specificity of the RIHA for "complicated" acute cholecystitis was 45%/100% and the positive/negative predictive value was 100%/39%. Liver tissue that was attached to the gallbladder by adhesions and removed at surgery was reviewed histologically and correlated with the presence or absence of a RIHA. The RIHA seems to be a useful indicator of patients presenting at a later stage of the pathologic spectrum of acute cholecystitis and perhaps at increased risk for complications.     

Morphine-augmented cholescintigraphy in acute cholecystitis. A satisfactory alternative to delayed imaging.

The utility of morphine-augmented cholescintigraphy was reviewed in 32 patients with suspected acute cholecystitis. All patients were administered 2 mg morphine sulfate intravenously when the gallbladder failed to visualize 30 minutes into the study, and imaging continued for up to 60 minutes. Sensitivity for detection of acute cholecystitis was 93% (13 out of 14). Specificity was 78% (14 out of 18). Three of four false-positives occurred in the setting of prolonged fasting and chronic cholecystitis. Cumulative experience suggests that the technique is diagnostically equivalent to imaging for up to 4 hours and that specificity remains incomplete in the setting of prolonged fasting, chronic cholecystitis and other conditions known to affect conventional cholescintigraphy.     

Role of cholecystokinetic agents in 99mTc-IDA cholescintigraphy

Cholecystokinin (CCK) and its C-terminal octapeptide analog, Sincalide, have been utilized in two separate roles for the evaluation of gallbladder disease. These are: (1) prior to cholescintigraphy to evacuate the gallbladder and optimized subsequent filling with radiotracers, and (2) to study contractile function of visualizing gallbladders on cholecystography and cholescintigraphy. As a preparation for 99mTc-IDA studies, it clearly facilitates earlier gallbladder filling in patients with chronic cholecystitis, thereby ruling out complete cystic duct obstruction. The problem lies in the fact that the use of CCK as a premedication markedly decreases the sensitivity of the study to detect chronic cholecystitis, since the findings become indistinguishable from patients with normal gallbladders. For this reason, the authors prefer to obtain delayed images, since chronic cholecystitis is frequently associated with gallbladder filling beyond the first hour. The role of CCK in detecting abnormal gallbladder function in the normally visualizing gallbladder also is controversial. Other studies as well as the author's experience suggests that as much as one-forth of positive cases may be associated with normal gallbladders at surgery and often even on microscopic examination. However, most importantly, the great majority of these patients are relieved of their symptoms following surgery. It appears reasonable that CCK or Sincalide cholecystography or cholescintigraphy may be detecting functional abnormalities before anatomic changes occur and can, therefore, serve as a useful examination in selecting symptomatic patients who may benefit from cholecystectomy.     

Cholecystokinin cholescintigraphy: methodology and normal values using a lactose-free fatty-meal food supplement.

The purpose of this investigation was to evaluate the use of a commercially available lactose-free fatty-meal food supplement, as an alternative to sincalide cholescintigraphy, to develop a standard methodology, and to determine normal gallbladder ejection fractions (GBEFs) for this supplement. METHODS: Twenty healthy volunteers all had negative medical histories for hepatobiliary and gallbladder disease, had no personal or family history of hepatobiliary disease, and were not taking any medication known to affect gallbladder emptying. All were prescreened with a complete blood cell count, comprehensive metabolic profile, gallbladder and liver ultrasonography, and conventional cholescintigraphy. Three of the 20 subjects were eliminated from the final analysis because of an abnormality in one of the above studies. RESULTS: After gallbladder filling on conventional cholescintigraphy, the subjects ingested the supplement and an additional 60-min study was acquired. GBEFs were calculated and ranged from 33% to 95% (mean +/- SD, 62.6% +/- 21.3%). Statistical analysis determined the lower range of normal to be 32.6%. Maximal gallbladder emptying occurred between 55 and 60 min. CONCLUSION: A standard methodology and normal GBEFs (> or =33%) were established for supplement-stimulated cholescintigraphy.     

The role of morphine-augmented cholescintigraphy and real-time ultrasound in detecting gallbladder disease

OBJECTIVE: Rapid diagnosis of acute cholecystitis is essential to minimize morbidity and mortality. The purpose of this study was to assess the diagnostic utility of cholescintigraphy using morphine augmentation compared with ultrasound, in acute and chronic gallbladder disease. METHODS: Cholescintigrams were performed on 103 patients suspected of having acute cholecystitis. In 79 patients (Group A) morphine sulfate was administered to reduce the scintigraphic imaging time if the gallbladder was not visualized during the first hour. In 24 control patients (Group B) no morphine was administered. All patients were evaluated clinically and 93 patients had concurrent ultrasound examination. RESULTS: The clinical presentation was nonspecific. The ultrasound findings were sensitive in detecting gallbladder disease (100%), but had low specificity (24%). Only findings of sediments and pericholecystic fluid were specific for cystic duct obstruction. Morphine augmentation reduced the imaging time by 126 min in patients with chronic cholecystitis. CONCLUSION: Real-time ultrasound has low specificity for gallbladder disease. In the presence of an abnormal ultrasound, it is essential to perform a hepatobiliary scan, either to exclude gallbladder disease or distinguish acute from chronic cholecystitis. Low-dose morphine administration is a safe and useful adjunct to standard cholescintigraphy by substantially reducing the time required to obtain a diagnostic study.     

A diagnostic dilemma of atypical gallbladder appearance on Tc-99m HIDA cholescintigraphy resolved with SPECT/CT

Tc-99m HIDA cholescintigraphy is the diagnostic procedure of choice for acute cholecystitis. Acute cholecystitis is associated in vast majority of the cases with cystic duct obstruction. The demonstration of presence (cystic duct patency) or absence (cystic duct obstruction) of visualization of the gallbladder on cholescintigraphy is critical to the diagnosis of acute cholecystitis. The visualization of the gallbladder rules out acute cholecystitis in most of the cases. Although, in most cases, determination of visualization or nonvisualization of gallbladder is straight forward, occasionally it can be challenging. We describe a patient with suspected acute cholecystitis, in whom an unusual appearance of the gallbladder on hepatobiliary scintigraphy was clarified with SPECT/CT, an approach that is rarely used in Tc-99m HIDA cholescintigraphy.     

Clinical efficacy of intravenous morphine administration in hepatobiliary imaging for acute cholecystitis

The most urgent diagnosis addressed by cholescintigraphy is acute cholecystitis. By administering low-dose intravenous morphine sulfate to patients undergoing cholescintigraphy (who demonstrate visualization of both the common bile duct and intestine and nonvisualization of the gallbladder), the time required to complete the study has been reduced to a maximum of 90 minutes. One hundred twenty-eight patients underwent cholescintigraphy for clinically suspected acute cholecystitis. Forty patients received intravenous morphine sulfate during the procedure. In patients who received morphine sulfate during the examination, the sensitivity of cholescintigraphy for the diagnosis of acute cholecystitis was 100%; the specificity was 85%.     

Scintigraphic evaluation of enterogastric reflux using 75Se-HCAT: methodology and first clinical observations

The aim of this study was to assess the possibility of detecting enterogastric reflux (EGR) by 75Se-HCAT cholescintigraphy. The lowest detectable activity in the gastric area at different concentrations of the radiotracer in the gallbladder was preliminary measured both in a plastic phantom and in an in vivo model. Ten patients were studied after a single oral administration of 1480 KBq 75Se-HCAT. Gamma camera imaging was carried out for five consecutive days during both fasting and after meal ingestion. In our in vivo model an EGR corresponding to 1% of gallbladder content on day one and 8% on day five was detected. In three out of five patients in whom bile was present in the stomach at endoscopy, 75Se-HCAT cholescintigraphy demonstrated an EGR, while in three out of five patients in whom endoscopy was negative, 75Se-HCAT cholescintigraphy detected EGR either during fasting or after meal ingestion. As EGR is not constant, 75Se-HCAT may be a useful tracer of bile to detect EGR over a prolonged period of time and in different physiological conditions.     

Incidence and significance of enterogastric reflux during morphine-augmented cholescintigraphy.

One hundred fourteen patients with suspected acute cholecystitis underwent morphine-augmented cholescintigraphy. The 115 studies were reviewed first to determine the incidence of enterogastric reflux under these conditions. Overall, enterogastric reflux was observed in 85/115 (74%), occurring only after intravenous morphine sulfate in the majority (59%, 50/85). Noted prior to morphine in 41% (35/85), the degree of enterogastric reflux increased noticeably directly following drug administration in over half of these cases. Surgical diagnoses were established in 73/114 (64%) patients as follows: 56 (77%) acute cholecystitis, 15 (20%) chronic cholecystitis, and 2 (3%) another entity (normal gallbladder and tumor encasement). These pathologically proven cases were examined more closely to address the diagnostic significance of enterogastric reflux during morphine-augmented cholescintigraphy. Enterogastric reflux was demonstrated in the majority of not only those with acute cholecystitis (48/56, 86%), but also those with chronic cholecystitis (12/15, 80%). A frequent but nonspecific finding, enterogastric reflux appears to be a pathophysiologic phenomenon that may be enhanced synergistically, at least to some degree, in patients requiring morphine-augmented cholescintigraphy.     

Simultaneous measurement of gallbladder emptying with cholescintigraphy and US during infusion of physiologic doses of cholecystokinin: a comparison

Both ultrasonography (US) and cholescintigraphy are used to study gallbladder dynamics. The present study was undertaken to determine whether the two methods provide the same or different information relating to gallbladder emptying. Emptying was simultaneously studied with both methods during infusion of graded physiologic doses of cholecystokinin (CCK) in six healthy subjects. Infusion of stepwise increasing doses of CCK, ranging from 0.03 to 0.5 Ivy dog units per kilogram of body weight per hour (IDU/kg.h), induced significant dose-related increases in plasma CCK, decreases in gallbladder volume assessed with US, and gallbladder emptying assessed with cholescintigraphy. The threshold dose for inducing significant gallbladder emptying was 0.13 IDU/kg.h, as determined with both techniques, indicating similar detection limits. There was a highly significant correlation between decreases in gallbladder volume and decreases in radioactive counts over the gallbladder region, with a tendency toward greater gallbladder responses at sonography during the early phase of gallbladder contraction and toward greater responses at cholescintigraphy during the later phase of gallbladder contraction. It is concluded that these methods can be used interchangeably for the quantitation of gallbladder emptying.     

Cholescintigraphic abnormality in a case of Kawasaki syndrome

A 26-month-old girl with Kawasaki syndrome (mucocutaneous lymph node syndrome) is presented. Liver function studies were abnormal and sonographic examination revealed hydrops of the gallbladder. The Tc-99m DISIDA cholescintigraphy demonstrated both early and delayed nonvisualization of the gallbladder. A photopenic area was noted in and below the gallbladder fossa and there was medial and upward displacement of the common bile duct. It appears that Kawasaki syndrome may result in nonvisualization of the gallbladder by cholescintigraphy. Accordingly, this diagnosis should be added to the list of conditions associated with nonvisualization of the gallbladder by biliary scintigraphy.     

Contribution of cholescintigraphy to the early diagnosis of acute acalculous cholecystitis in intensive-care-unit patients.

Thirty-two intensive care unit patients (78% on long-term total parenteral nutrition) suspected of having acute acalculous cholecystitis (AAC) were studied prospectively. All of these patients underwent abdominal ultrasonography and cholescintigraphy with technetium-99m mebrofenin. Morphine sulphate (0.04 mg/kg) was administered only if the gallbladder was not visualised after 1 h (16 patients). The final diagnosis was reached after clinical improvement, or upon the discovery of another aetiology for the symptoms presented, or on the basis of histopathology following cholecystectomy (when this was performed). We analysed the contribution of individual cholescintigraphic findings (I: non-visualisation of the gallbladder during the first 60 min of the examination; II: persistent non-visualisation of the gallbladder 30 min following morphine administration; III: non-visualisation of the small bowel for at least 90 min) and their various combinations. We obtained a sensitivity of 79% and a specificity rate 100% using the interpretative criteria "I and II or III". Excluding obstructive syndrome ("I and II"), the sensitivity and specificity figures were 70% and 100% respectively (28 patients). We had no false-positive results in our patient population. Cholescintigraphy was found to complement ultrasonography, which had either good sensitivity (93%) and poor specificity (17%), when at least two of the three major signs were present (sludge, thickened wall, gallbladder distension), or poor sensitivity (36%) and good specificity (89%) when all three signs were present. We conclude that cholescintigraphy is a useful tool for early diagnosis of AAC in critically ill patients, in whom ultrasonography alone does not provide enough information to permit a sufficiently early decision regarding the use of surgery.     

Cholescintigraphy in gallbladder carcinoma

Findings on cholescintigraphy in gallbladder carcinoma are described in five patients. Four patients presenting with acute cholecystitis had nonvisualization of the gallbladder with normal hepatoenteric transit time. One of these had a large portal mass and two had liver metastasis as additional findings. The fifth patient was jaundiced, and showed absence of bowel activity compatible with total biliary obstruction. Both the clinical and scintigraphic findings in gallbladder carcinoma are difficult to separate from findings in cholelithiasis and cholecystitis.     

Cholecystokinin cholescintigraphy: detection of abnormal gallbladder motor function in patients with chronic acalculous gallbladder disease

CCK cholescintigrams were performed in 374 patients with recurrent postprandial right upper quadrant pain, biliary colic, and a normal gallbladder sonogram and/or cholecystogram. The results of these examinations were correlated with the patients' final medical/surgical diagnoses. Twenty-seven patients recruited as control volunteers without objective clinical evidence of biliary disease also underwent CCK cholescintigraphy to determine if the degree of gallbladder contraction post-CCK differs in symptomatic versus asymptomatic subjects. Decreased gallbladder motor function was identified (maximal gallbladder ejection fraction response to CCK less than 35%) in 94% of patients with histopathologically confirmed chronic acalculous cholecystitis or the cystic duct syndrome and in 88% of patients clinically believed to have chronic acalculous biliary disease. Decreased gallbladder motor function does not distinguish symptomatic from asymptomatic gallbladder disease.     

Cholecystokinin cholescintigraphy: clinical indications and proper methodology

Cholecystokinin is a useful diagnostic adjunct to cholescintigraphy. Clinical indications include contracting the gallbladder before cholescintigraphy in patients fasting greater than 24 hours, during cholescintigraphy to diagnose sphincter of Oddi dysfunction, and after cholescintigraphy to exclude acute acalculous cholecystitis, differentiate common duct obstruction from normal variation, and to confirm the diagnosis of chronic acalculous cholecystitis. Proper methodology is mandatory for a diagnostically useful test. Data presented shows that a 3-minute infusion of 0.01 or 0.02 microg/kg is nonphysiologic and often results in ineffective contraction similar to that seen with a bolus infusion. Normal gallbladder ejection (GBEF) values cannot be established using a 3-minute infusion because of the wide variability in response. Instead, infusions of 30 or 60 minutes are required. Normal GBEF values have been established for these methods and are 30% and 40%, respectively.     

Cholecystokinin cholescintigraphy: victim of its own success?

Numerous publications have reported that a low gallbladder ejection fraction (GBEF) determined by cholecystokinin (CCK) cholescintigraphy has a high positive predictive value for the diagnosis of chronic acalculous cholecystitis (CAC). Clinicians and surgeons have found this test to be clinically useful as an objective method to confirm their clinical diagnosis. However, an abnormally low GBEF is not specific for CAC. For example, numerous other diseases have been associated with a low GBEF, and various therapeutic drugs can cause poor gallbladder contraction. Importantly, improper CCK infusion methodology can result in an erroneously low GBEF. More than one third of healthy subjects and patients who receive sincalide, 0.02 microg/kg infused over 1-3 min, will have an erroneously low GBEF but will have a normal GBEF with a slower infusion (30-60 min) of the same total dose. Because of enthusiastic acceptance of CCK cholescintigraphy by clinicians, the types of patients referred for this test have changed over time. Patients investigated in publications confirming the usefulness of CCK cholescintigraphy had a high pretest likelihood of disease. They underwent extensive workup to rule out other diseases and were followed up for months or years before CCK cholescintigraphy was performed, allowing other diseases to become manifest or symptoms to resolve. However, CCK cholescintigraphy is now being used by clinicians to shorten the workup and follow-up time based on the rationale that CCK cholescintigraphy can quickly confirm or exclude the diagnosis. This new group of referral patients has a lower likelihood of the disease. Many will ultimately be diagnosed with diseases other than CAC. The positive predictive value of this test will likely be lower and the false-positive rate will likely be higher. Nuclear medicine physicians must work to minimize false-positive studies to maintain the confidence of referring clinicians. First, we can educate referring physicians as to the proper use of this study. Next, we must perform CCK cholescintigraphy using optimal methodology that will result in the lowest possible false-positive rate. And finally, we must interpret CCK cholescintigraphy in light of the patient's history, prior workup and clinical setting.     

Technetium-99m-pyridoxylideneglutamate: a new hepatobiliary radiopharmaceutical. II. Clinical aspects.

Technetium-99m-pyridoxylideneglutamate (99mTc-PG) is a nontoxic radiopharmaceutical that was found to undergo rapid biliary excretion in normal humans. The biliary tree and gallbladder were seen within 10-15 min of injection and by 20 min marked accumulation of radioactivity was noted in the gallbladder and gastrointestinal tract. Of ten "control" volunteers, seven had normal 99mTc-PG-cholescintigrams. In the remaining three, the gallbladder was not visualized. Gallbladder disease was not excluded in these three subjects. Of 24 patients referred for investigation of right upper quadrant abdominal pain, 13 proved to have gallbladder disease. All seven patients with acute cholecystitis and one of four patients with chronic cholecystitis had nonvisualization of the gallbladder on the cholescintigram whereas five patients with chronic cholecystitis or cholesterolosis had normal cholescintigrams. Six of the eight patients with nonvisualization of the gallbladder on cholescintigram had contrast radiologic studies (oral cholecystogram or intravenous cholangiogram or both), and in all six, nonvisualization of the gallbladder was also reported on the contrast study. cholescintigraphy was found to be greatly inferior to contrast radiologic studies in the detection of gallbladder stones.Eleven patients had complete extrahepatic biliary obstruction and this diagnosis was correctly made in all 11 by the cholescintigram. Fourteen patients had incomplete extrahepatic biliary obstruction. The correct diagnosis was made on the cholescintigram in seven but in the remaining seven it was not possible to distinguish between incomplete extrahepatic biliary obstruction and hepatocellular disease. Malignant lesions (carcinomas of head of pancreas, gallbladder, common bile duct or ampulla of Vater) were the cause of obstruction in 10 of the 25 patients with complete or incomplete obstruction and the diagnosis of obstruction due to malignancy was correctly made in 8 of these 10 by means of a scintigraphic equivalent to Courvoisier's sing. Finally, 11 patients had hepatocellular disease and a nonspecific pattern consistent with either imcomplete biliary obstruction or hepatocellular disease was observed on the cholescintigram in all 11. The 99mTc-PG cholescintigram is suggested for a role complementary to that of contrast radiologic studies in the preoperative investigation of patients with possible surgical disease of the biliary tract. Contrast radiologic techniques are advocated as being more appropriate in the nonjaundiced patient with suspected gallbladder disease whereas the 99mTc-PG cholescintigram is advocated as being more appropriate in the patient with jaundice. The value of the 99mTc-PG cholescintigram lies in the confidence with which complete extrahepatic biliary obstruction can be diagnosed. The "scintigraphic Courvoisier's sign" seems a useful indicator of malignant obstruction.     

Quantitative cholescintigraphy and bile abnormalities in patients with acalculous biliary pain

Acalculous biliary pain has been related to gallbladder dysfunction that produces a gallbladder emptying defect—a condition which favours the development of lithiasis. It is therefore probable that microlithiasis is present in patients with gallbladder dysfunction. The aims of this study were to measure gallbladder emptying and investigate bile abnormalities in patients with acalculous biliary pain. In 92 consecutive patients, gallbladder emptying was assessed by quantitative cholescintigraphy (abnormal ejection fraction 40%). In 64 patients, a microscopic study was performed on duodenal bile, defining abnormality as the presence of cholesterol crystals in any amount and/or calcium bilirubinate granules and/or microspheroliths at a rate of >10 per slide. The ejection fraction was abnormal in 45 patients (49%) (median 25.1%, range 6.8–39.3%) and normal in the remaining 47 cases (median 71.3%, range 41.0–96.1%). Bile was abnormal in 32 of 64 patients (50%), the most frequent finding being calcium bilirubinate granules. In the patients with bile abnormalities, abnormal ejection fraction was more frequent (20 of 32) and the median ejection fraction was lower (30.9%, range 12.0–94.1%) than in the patients with normal bile (16 of 32 with an abnormal ejection fraction; median ejection fraction 50.7%, range 6.8–96.1%). Abnormal bile was frequent (55.5%) in patients with reduced ejection fraction, but was not uncommon in patients with normal ejection fraction (33.3%). Fewer patients showed no alteration (25%). It is concluded that in most patients, acalculous biliary pain coexists with gallbladder dysfunction or abnormal bile, the combination of both alterations being common.